Transitional cell neoplasms of the human urinary tract are often multifocal, have a high frequency of recurrences, and may evolve into invasive fatal disease. The clinical course of patients initially presenting with noninvasive transitional cell carcinomas (TCCs) is often unpredictable on the basis of conventional morphologic criteria. Recent studies have indicated that the tumor tissue reactivity for the A,B, or H blood group antigen(s) may be useful in predicting the subsequent course. We plan a prospective longitudinal study of the expression of known blood group antigens (A,B,H, LEa, LEb, M, N, T, I, and i) in the neoplastic as well as the normal appearing urothe-lium of patients with TCCs. Multiple serial biopsies from TCCs and morphologically normal mucosa will be evaluated using the red cell adherence and/or immunoperoxidase techniques in order to identify patterns of antigenic changes predictive of the tumor's biologic behavior. Altered reactivity, quantitative and/or qualitative, for one or more of these antigens will be correlated with the presence of multifocal urothelial neoplasms, recurrence rate, and propensity for invasion. The antigenic abnormalities will also be correlated with ultrastructural changes as viewed by transmission and scanning electron microscopy. These studies have both conceptual and practical significance: (1)\they will help evaluate the concept of "field" phenomenon, the "preneoplastic" state, and the interrelationship of antigenic and morphologic changes in the evolution of urothelial neoplasia; and (2)\they may identify clinically applicable predictive parameters. (2)